LGR4 expressed in uterine epithelium is necessary for uterine gland development and contributes to decidualization in mice

TY - JOUR

T1 - LGR4 expressed in uterine epithelium is necessary for uterine gland development and contributes to decidualization in mice

AU - Sone, M.

AU - Oyama, K.

AU - Mohri, Y.

AU - Hayashi, R.

AU - Clevers, H.

AU - Nishimori, K.

N1 - Reporting year: 2013

PY - 2013

Y1 - 2013

N2 - In previous work we generated mice with a tissue specific ablation of a leucine-rich repeat containing G-protein-coupled receptor 4 (Lgr4) using the Keratin-5 (K5) Cre transgenic mouse strain (Lgr4(K5 KO)). Interestingly, the Lgr4(K5 KO) female mice were subfertile, and their embryos had impaired development. Notably, the contributions of uterine development to the subfertility phenotype were not elucidated in the previous report. In a readdress, the following study explores uterine aberration in Lgr4(K5 KO) female mice. Histological analysis revealed that the uteri of Lgr4(K5 KO) mice displayed altered epithelial differentiation characterized by a reduction in the number of uterine glands. Furthermore, Lgr4 deletion led to the reduced expression of morphoregulatory genes related to the Wnt signaling pathway. Additionally, the uteri of the Lgr4(K5 KO) mice lost the ability to undergo induced decidualization. Quantitative reverse transcription-polymerase chain reaction (qRT-PCR) analysis and administration of recombinant leukemia inhibitory factor (LIF) demonstrated that the impaired decidualization in Lgr4(K5 KO) mice resulted from the decreased secretion of LIF concurrent with a reduction in uterine gland count. Thus, we propose that LGR4 contributes to uterine gland development, which supports decidualization during pregnancy.-Sone, M., Oyama, K., Mohri, Y., Hayashi, R., Clevers, H., Nishimori, K. LGR4 expressed in uterine epithelium is necessary for uterine gland development and contributes to decidualization in mice.

AB - In previous work we generated mice with a tissue specific ablation of a leucine-rich repeat containing G-protein-coupled receptor 4 (Lgr4) using the Keratin-5 (K5) Cre transgenic mouse strain (Lgr4(K5 KO)). Interestingly, the Lgr4(K5 KO) female mice were subfertile, and their embryos had impaired development. Notably, the contributions of uterine development to the subfertility phenotype were not elucidated in the previous report. In a readdress, the following study explores uterine aberration in Lgr4(K5 KO) female mice. Histological analysis revealed that the uteri of Lgr4(K5 KO) mice displayed altered epithelial differentiation characterized by a reduction in the number of uterine glands. Furthermore, Lgr4 deletion led to the reduced expression of morphoregulatory genes related to the Wnt signaling pathway. Additionally, the uteri of the Lgr4(K5 KO) mice lost the ability to undergo induced decidualization. Quantitative reverse transcription-polymerase chain reaction (qRT-PCR) analysis and administration of recombinant leukemia inhibitory factor (LIF) demonstrated that the impaired decidualization in Lgr4(K5 KO) mice resulted from the decreased secretion of LIF concurrent with a reduction in uterine gland count. Thus, we propose that LGR4 contributes to uterine gland development, which supports decidualization during pregnancy.-Sone, M., Oyama, K., Mohri, Y., Hayashi, R., Clevers, H., Nishimori, K. LGR4 expressed in uterine epithelium is necessary for uterine gland development and contributes to decidualization in mice.

U2 - 10.1096/fj.13-232215

DO - 10.1096/fj.13-232215

M3 - Article

SN - 0892-6638

VL - 27

SP - 4917

EP - 4928

JO - FASEB Journal

JF - FASEB Journal

IS - 12

ER -